Peripheral neuropathy is a frequent consequence of exposure to toxic chemicals; neurofilamentous axonpathy is produced by exposure to acrylamide (ACR), hexacarbons (HXC), 3,3' iminodipropionitrile (IDPN). Determination of the doses and mechanism(s) of action of these compounds will allow accurate determination of permissable exposure limits, outline preventive measures, and possibly develop cures. This information is useful in the search for causes of other neuropathological conditions. We hypothesize that nerve degeneration observed in ACR and HXC neuropathies is due to block of fast axoplasmic transport, IDPN is used as a negative contorl. Since fast axoplasmic transport is dependent upon the microtubule, our focus is upon the effects of these toxicants upon this cytoskeletal element. We will determine the time frame and dose response of changes in axoplasmic transport following single injections of ACR,HXC and/or IDPN and determine whether these changes are caused by disassembly of microtubles in vivo and/or in vitro using immunofluorescence of cultured mouse Balb 3T3 cells with specific monoclonal antibodies, turbidity assays, biochemical analysis of polymerized vs non-polymerized tubulin and electron microscopy. Disruption of mitosis and axoplasmic transport in vivo and assembly of tubulin into microtubules in vitro by specific doses of the toxicants will be measured. Correlation of the altered axoplasmic transport rate and capacity with microtubule disruption will be conducted. We will determine whether or not these toxicants directly bind to the colchicine and/or vinblastine binding sites, whether they affect microsomal ATPase activity and whether tyey crosslink tubulin using western blots and specific monoclonal antibodies. The data gathered by these investigations will determine whether or not microtubule structural alteration or dissembly by the neurotoxicants is related to microtubule dysfunction and may determine the mechanism by which this action is mediated.